This invention relates to a process for preparing known active nitro, trifluoromethyl containing diphenylether herbicides having the formula: ##STR1## wherein X is hydrogen, halo such as chloro, bromo, fluoro and the like; trihalo lower alkyl such as trifluoromethyl and the like; lower alkyl such as methyl, ethyl, propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, and the like, X' is selected from hydrogen, halo, such as chloro, bromo, fluoro and the like, cyano, lower alkyl such as methyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl and the like; lower alkoxy such as methoxy, ethoxy, iso-propoxy, butoxy, pentoxy and the like; carboxy; carbalkoxy such as carbomethoxy, carboethoxy, carbo-iso-propoxy, carbo-tert-butoxy, carbo-n-pentoxy, and the like; carbalkoxyalkoxy such as 1-carboethoxyethoxy, 1-carbomethoxypropoxy and the like; carbamoyl; mono- and di-lower alkyl substituted carbamoyl such as N-methylcarbamoyl, N-iso-propylcarbamoyl, N-n-butylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl and the like; substituted alkoxycarbonyl such as 2-methoxyethoxycarbonyl, 2-ethoxypropoxycarbonyl, 2-iso-butoxyethylcarbonyl and the like; alkenyloxycarbonyl such as 2-propenyloxycarbonyl, 2-(2-methylpropenyloxy)carbonyl and the like; or trifluoromethyl and X" is halo or trifluoromethyl with the proviso that when X" is halo X is trifluoromethyl.
The following U.S. patents disclose trifluoromethyl substituted diphenylethers U.S. Pat. Nos.: 3,798,276; 3,928,416; 4,031,131; 4,063,929; 3,784,635; 4,087,272; 4,002,662; 4,001,005; 3,983,168; 3,979,437; 3,941,830; 3,907,866; 3,873,302; 3,954,829; 3,839,444; 3,957,865; 4,017,300, and 3,862,209.
A key intermediate in the synthesis of the diphenyl ether (I, supra) is the substituted or unsubstituted trifluoromethylphenol. There are various routes to this compound. See for example U.S. Pat. Nos. 3,888,932; 3,772,344; 3,819,755 and references cited therein. The present processes either involve too many steps or are economically unattractive or both. [See Mooradian, et al., J. Am. Chem. Soc., 73, 3470-2 (1951; McBee et al., J. Am. Chem. Soc., 73, 1325-6 (1951); Jones, R. G., J. Am. Chem. Soc., 69, 2346-50 (1947); and Lavagnino, E. R., et al., Org. Preparations and Procedures International, Vol. 9, pps 96-98 (1977).]
The basic problem in the preparation of a trifluoromethyl phenol is the sensitivity of the trifluoromethyl radical to not only concentrated but even dilute base. (See Jones, R. G., J. American Chemical Society, 69, 2346-50 (1947)).
It has now been discovered that by employing a special solvent system to regulate the amount of base in solution and reduce the presence of water, trifluoromethylphenates can be produced in a single step in good yield, in situ. The corresponding trifluoromethylphenols can be isolated upon acidification, or condensed directly with appropriately substituted halo nitrobenzenes to afford herbicidal diphenyl ethers or precursors thereof.
The following equation illustrates this process for preparing trifluoromethylphenol from a chloro substituted compound however, it is to understood that in place of the chloro radical, a fluoro radical could also be used; ##STR2## wherein X is as defined above and M is a cation derived preferentially from an alkali metal or alternatively from an alkaline earth metal. Hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, and the like may be employed with sodium being a preferred cation and potassium the most preferred cation. The reaction is conducted at a temperature in the range of from about 50.degree. to about 100.degree. C. and, preferably, in the range of from about 65.degree. to about 85.degree. C. for a period of time preferably in the range of from 5 hours to 5.5 days and most preferably in the range of from 10 to 55 hours. It is understood that some product is formed within several hours, however, the time periods set forth above represent the optimum time periods. The reaction is generally conducted at atmospheric pressure. Other halobenzenes (III, supra) include ##STR3## wherein X and X" are as defined above and X.sup.2 is fluro or chloro.
A key element in this invention is the cosolvent system which is prepared from a dipolar, aprotic solvent and a non-nucleophilic, hydroxylated cosolvent.
Dipolar, aprotic solvents employed in this invention include solvents having dielectric constants in the range of from about 30 to about 70 which solvents are inert or substantially inert to the base employed. Examples of the preferred dipolar, aprotic solvents include dimethyl sulfoxide, tetrahydrothiophene-1,1-dioxide, hexamethylphosphoric triamide and the like.
The non-nucleophilic, hydroxylated cosolvent which provides for increased solubility of the metal hydroxide is believed to impart stability by hydrogen bonding with the formed 4-trifluoromethylphenolate salt.
Non-hindered alcohol such as methanol, ethanol, n-propanol or iso-propanol, however, may enter into competitive reactions with the 4-trifluoromethylphenolate resulting in formation of undesired by-products. Less nucleophilic n-alcohols (C.sub.4 and above) are more desirable as cosolvents than the C.sub.1 -C.sub.3 alcohols, listed above.
The hydroxylated cosolvents employed in this invention are those having the following structural formla: ##STR4## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are the same or different groups selected from hydrogen; straight or branched lower alkyl, substituted or unsubstituted phenyl wherein the phenyl substituents may be alkyl, halo, lower alkoxy, or benzyl, and the like; R.sup.8 is lower alkyl; n and n.sup.2 are 0 or 1; n.sup.1 is 0 to 2, n.sup.3 is an integer of from 1 to 10; n.sup.4 is 2 to 4 provided that n.sup.1 is 2 only when n and n.sup.2 are both 0, otherwise the sum of n.sup.1 and n.sup.2 may not be greater than 1; when n.sup.3 is greater than 2, the sum of n and n.sup.2 may not simultaneously be greater than 1 and n.sup.1 must be 0; when R.sup.7 is hydrogen, n.sup.1 must be zero and the sum of n and n.sup.2 must be 1 such that at least 3 of the groups R, R' plus either the pair R.sup.2 and R.sup.3 or the pair R.sup.5 and R.sup.6 must not be hydrogen.
Examples of the hydroxylated solvents include tert-butyl alcohol, pinacol, pentaerythritol, 2,4-dimethyl-2,4-pentanediol, 2,4-dimethyl-2,3,4-pentanetriol, 2,4-dimethyl-1,2-pentanediol, 2,4-dimethyl-3-pentanol, 2,2,4-trimethyl-3-pentanol, 2,2-dimethyl-1-propanol, ##STR5## 1-methyl-1-cyclohexanol, 2-iso-propyl-1-cyclopentanol and the like.
The cosolvents are employed at a ratio in the range of from about 1 to about 30 parts of the non-nucleophilic hydroxylated cosolvent to about 100 parts of the dipolar, aprotic solvent and preferably at a ratio in the range of from about 5 to about 20 parts of the non-nucleophilic solvent to about 100 parts of the dipolar, aprotic solvent.
The free phenol (II, below) may be isolated by treatment with acid or may be reacted with an appropriately substituted halobenzene to afford either a diphenyl ether herbicide or precursor which may be reacted further to afford the desired diphenyl ether (I, supra).
This procedure is illustrated by the following: ##STR6## wherein M, X, X' and X" are as defined above and halo is preferably chloro or fluoro. Fluoro is preferred for enhancing reaction rates while chloro is preferred in terms of lower raw material costs.
The following illustrates in greater detail the preparation of the preferred diphenyl ether herbicides however, it is to be understood that other products falling within the generic description (I, supra) may also be prepared in a similar manner: ##STR7## wherein X, X' and M are as defined above. Especially preferred are those compounds where X is hydrogen or chloro and X.sup.1 is lower alkyl, lower alkenyl, or lower alkoxyalkyl esters or alkyl or dialkyl amides thereof. The lower alkyl esters can be readily hydrolyzed under acidic or basic conditions to afford the carboxylic acid which can readily be converted to alkali or alkaline earth metal salts or to various amine salts as desired.
The reaction between the trifluoromethylphenolate (II supra) and the halonitrobenzene (IV, supra) is generally conducted at a temperature in the range of from about 25.degree. to 130.degree. C. and preferably in the range of from about 25.degree.-85.degree. C. when the halo is fluoro and 60.degree.-130.degree. C., preferably 65.degree.-85.degree. C., when the halo is chloro. Dipolar, aprotic solvents which may be employed include dimethylsulfoxide, dimethylformamide, tetrahydrothiophene 1,1-dioxide, hexamethylphosphoric triamide, N-methylacetamide, ethylene carbonate, dimethoxy ethane, 1,4-dioxane and the like. Non-nucleophilic, hydroxylated cosolvents described above may advantageously be employed at 1-10 parts per 100 parts of the dipolar, aprotic solvent. If the free phenols (IIa or IId) are employed, the reaction must be conducted in the presence of an alkali metal or alkaline earth metal base such as anhydrous hydroxides, carbonates, bicarbonates and the like; preferred alkali metals are potassium and sodium.
Synthesis of 5-chloro-2-nitrobenzoates (i.e., X is carboxy) are described in Beilstein, IX, p. 401 and may be represented as follows: ##STR8## wherein R.sup.1 is hydrogen or lower alkyl.
The synthesis of 5-fluoro-2-nitrobenzoic acid from 3-fluorobenzoic acid has been described by J. H. Slothouwer, Rec. trav. chim., 33, 324-42, 1914.